Latent and active p53 are identical in conformation

p53 is a nuclear phosphoprotein that regulates cellular fate after genotoxi c stress through its role as a transcriptional regulator of genes involved in cell cycle control and apoptosis. The C-terminal region of p53 is known to negatively regulate sequence specific DNA-binding of p53; modifications to the C-terminus relieve this inhibition. Two models have been proposed to explain this latency: (i) an allosteric model in which the C-terminal doma in interacts with another domain of p53 or (ii) a competitive model in whic h the C-terminal and the core domains compete for DNA binding. We have char acterized latent and active forms of dimeric p53 using gel mobility shift a ssays and NMR spectroscopy. We show on the basis of chemical shifts that di meric p53 both containing and lacking the C-terminal domain are identical i n conformation and that the C-terminus does not interact with other p53 dom ains. Similarly, NMR spectra of isolated core and tetramerization domains c onfirm a modular p53 architecture. The data presented here rule out an allo steric model for the regulation of p53.